Intravenous Levosimendan and Vasopressin in New-Onset Acute Pulmonary Hypertension After Weaning from Cardiopulmonary Bypass.

OBJECTIVE: A novel treatment with intravenous levosimendan and vasopressin for new-onset acute pulmonary hypertension after weaning from cardiopulmonary bypass is described. DESIGN: Retrospective analysis of a case series. SETTING: Single-center study. PARTICIPANTS: Nineteen patients undergoing cardiac surgery exhibited new-onset acute pulmonary hypertension with acute right ventricular dysfunction after cardiopulmonary bypass. INTERVENTION: Pulmonary hypertension with acute right heart dysfunction was treated with levosimendan as inodilator therapy and vasopressin combined with norepinephrine for systemic vasopressor therapy. MEASUREMENTS AND MAIN RESULTS: Mean pulmonary artery pressure decreased from 32 ± 9 to 26 ± 6 mmHg (p = 0.039) in the first 24 hours along with an increase in cardiac output (3.2 ± 1 to 4.2 ± 1.1 L/min; p = 0.012) and resolution of lactic acidosis. The ratio between mean pulmonary artery pressure and mean arterial pressure decreased from 1:2 to 1:3, and Wood units decreased from 3 ± 1 to 1.5 ± 2 (p = 0.042). At 30 days after intervention, 3 patients died. CONCLUSION: The combination of levosimendan for inotropic support of the right ventricle in conjunction with its vasodilatory effect on the pulmonary circulation, along with the combination of vasopressin and norepinephrine for systemic vasopressor therapy, may be an effective alternative for the treatment of acute new-onset pulmonary hypertension and acute right heart dysfunction after cardiopulmonary bypass. Although there are many confounding variables in this case series, these findings justify additional sufficiently powered trials.

Vasopressin in Cardiac Surgery: A Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: To summarize the results of randomized controlled trials on the use of vasopressin as a vasopressor agent in cardiac surgery. DESIGN: Meta-analysis. PARTICIPANTS: Six-hundred-twenty-five adult patients undergoing elective or emergency cardiac surgery. INTERVENTIONS: Arginine vasopressin infusion (n = 313) or control/standard therapy (n = 312). MEASUREMENTS AND MAIN RESULTS: The rates of perioperative complications and postoperative mortality were used as primary and secondary endpoints, respectively. Fixed and/or random effects models were used to compare pooled odds ratios. Arginine vasopressin reduced the pooled odds ratio (OR) of perioperative complications (OR, 0.33; 95% confidence interval [CI], 0.2-0.54; p < 0.0001). A sensitivity analysis excluding the largest trial showed an unchanged reduction in perioperative complications (OR, 0.35; 95% CI, 0.18-0.69; p = 0.002). When analyzing each perioperative complication separately, vasopressin reduced the pooled OR of vasodilatory shock (OR, 0.4; 95% CI, 0.16-0.97; p = 0.04) and new-onset atrial fibrillation (OR, 0.42; 95% CI, 0.21-0.82; p = 0.01). The pooled OR of postoperative death was not different between patients treated with arginine vasopressin and those receiving standard therapy or placebo (OR, 0.83; 95% CI, 0.45-1.53; p = 0.55). The funnel plot for the primary endpoint suggested a relevant publication bias. All included trials suffered from a high risk of bias. CONCLUSION: Our meta-analysis suggests that arginine vasopressin may reduce the rate of perioperative complications in patients undergoing elective or emergency cardiac surgery. No difference in postoperative mortality was observed. An adequately powered multicenter trial is required for reliable estimation of the effects of arginine vasopressin on perioperative complication rates and mortality in cardiac surgical patients.

The impact of endotoxin on jejunal tissue oxygenation.

OBJECTIVE: We examined the effects of systemic ETX on jejunal mucoal microcirculatory parameters in anesthetized pigs. METHODS: Jejunal mucosal tissue PO2 was measured employing Clark-type surface oxygen electrodes. Oxygen saturation of jejunal microvascular hemoglobin was determined by tissue reflectance spectrophotometry. Jejunal microcirculatory blood flow was assessed by laser Doppler flowmetry. Microvascular conductance and rhythmical oscillation of the tissue PO2 were calculated. Systemic hemodynamic variables, mesenteric venous and systemic acid base and blood gas variables, and lactate measurements were recorded. Measurements were taken at BL and after Escherichia coli LPS administration in 20 minutes intervals for 110 minutes. RESULTS: ETX infusion led to a significant (P<.05) decrease of PO2 muc (from 24±4 to 8±4 mm Hg) and microvascular HbO2 (from 41±13 to 24±12%). Microcirculatory conductivity increased in ETX animals, microvascular blood flow remained unchanged (PU; from 228±45 to 232±58). ETX induced an increase in oscillation frequency of mucosal tissue oxygenation. CONCLUSIONS: Endotoxinemia resulted in a significant depression of mucosal tissue oxygenation despite a constant microcirculatory blood flow. This impairment of tissue oxygenation resulted in an increase in the vasomotion pattern in a futile attempt to counteract the undersupply of oxygen to the jejunal tissue.

Pulmonary function after emergence on 100% oxygen in patients with chronic obstructive pulmonary disease: a randomized, controlled trial.

BACKGROUND: During emergence from anesthesia, breathing 100% oxygen is frequently used to provide a safety margin toward hypoxemia in case an airway problem occurs. Oxygen breathing has been shown to cause pulmonary gas exchange disorders in healthy individuals. This study investigates how oxygen breathing during emergence affects lung function specifically whether oxygen breathing causes added hypoxemia in patients with chronic obstructive pulmonary disease. METHODS: This trial has been conducted in a parallel-arm, case-controlled, open-label manner. Fifty-three patients with chronic obstructive pulmonary disease were randomly allocated (computer-generated lists) to breathe either 100 or 30% oxygen balanced with nitrogen during emergence from anesthesia. Arterial blood gas measurements were taken before induction and at 5, 15, and 60 min after extubation. RESULTS: All participants tolerated the study well. Patients treated with 100% oxygen had a higher alveolar-arterial oxygen pressure gradient (primary outcome) compared with patients treated with 30% oxygen (25 vs. 20 mmHg) and compared with their baseline at the 60-min measurement (25 vs. 17 mmHg). At the 60-min measurement, arterial partial pressure of oxygen was lower in the 100% group (62 vs. 67 mmHg). Arterial partial pressure of carbon dioxide and pH were not different between groups or measurements. CONCLUSIONS: In this experiment, the authors examined oxygen breathing during emergence-a widely practiced maneuver known to generate pulmonary blood flow heterogeneity. In the observed cohort of patients already presenting with pulmonary blood flow disturbances, emergence on oxygen resulted in deterioration of oxygen-related blood gas parameters. In the perioperative care of patients with chronic obstructive pulmonary disease, oxygen breathing during emergence from anesthesia may need reconsideration.

The physiologic perspective in fluid management in vascular anesthesiology.

Vascular surgery patients frequently suffer from atherosclerosis and peripheral arterial occlusive disease generating endothelial dysfunction. Furthermore, ischemia and reperfusion during surgery damage endothelial cells and, especially, the endothelial glycocalix. The damage of the glycocalix promotes an increase in permeability. Not only crystalloids, which freely diffuse between the intravascular and the interstitial compartment, but also colloidal fluids cross from the intravascular space in the interstitial space with the consequence of edema formation. Possible tissue edema may result in an impairment of tissue oxygenation, leading to wound healing disturbances and initiation of inflammatory responses up to tissue apoptosis. Particularly in vascular anesthesia, this possibly means that colloids only should be administered in acute volume resuscitation immediately after unclamping a big vessel for immediate volume restoration. Which colloidal fluid should be administered is still under intense discussion. From a theoretical physiologic point of view, iso-osmolar albumin is the best choice regarding volume effect, antioxidative properties, and protection against destruction of the glycocalix. Nonetheless, albumin experimentally has not lived up to its promise in the clinical setting. Thus, further well-conducted large randomized clinical trials are necessary to ascertain the optimal fluid therapy in vascular surgery patients.

Preoperative identification of patients with increased risk for perioperative bleeding.

PURPOSE OF REVIEW: Although the overall complication rate in cardiac surgery has been decreased, perioperative bleeding increasing morbidity and mortality is still frequent. Furthermore, the widespread use of new antithrombotic and antiplatelet agents presents an additional challenge in daily practice. Therefore, identifying patients with increased bleeding risk would be advantageous to optimize perioperative management. RECENT FINDINGS: Bleeding classifications are frequently discussed, but are of little relevance for the perioperative setting. In the nonsurgical setting the most relevant risk factors in bleeding prediction are age, renal disease, sex, pre-existing anemia, and the administration of antithrombotic/antiplatelet drugs. In cardiac surgery, the Papworth Bleeding Risk Stratification Score identifies mainly procedure-linked risk factors and might be one of the most suitable scores to be used. Routine laboratory screening appears to have limited utility. SUMMARY: Apart from precise bleeding history only insufficient data exist in cardiac surgery to exactly predict bleeding complications. Therefore, there is urgent need for further studies to improve perioperative bleeding management.

Carry-Over Quality of Pre-acclimatization to Altitude Elicited by Intermittent Hypoxia: A Participant-Blinded, Randomized Controlled Trial on Antedated Acclimatization to Altitude.

Intermittent normobaric hypoxia (IH) is increasingly used to pre-acclimatize for a sojourn to high altitude. There is a number of hypoxia - protocols observing the hypoxic ventilatory response (HVR), but little is known about the carry - over quality of the Lake Louise Score (LLS). We thus studied a week - long, 1 h per day poikilocapnic hypoxia protocol on whether acclimatization could be carried over for one week. Rationale for this was that it usually takes one week to get from Europe, Britain or the United States to the base camp of a major mountain. Forty-nine healthy volunteers of both sexes were exposed to daily bouts of 1 h at an inspiratory fraction of oxygen (FiO2) of 0.11 or 0.21 (control) for 7 consecutive days. Seven days after cessation of IH or sham exposures participants were again subjected to hypoxia (FiO2 = 0.11) for 6 h and measurements of isocapnic HVR and blood gases out of the arterialized earlobe were taken and LLS was assessed. In those with IH exposures LLS was reduced which was not the case in those with sham exposure (87 vs. 50%). Changes in HVR or the arterial hemoglobin saturation were not observed. Gender neither affected LLS nor HVR nor blood gases or carry -over quality. We found that our week - long, hypoxia protocol grants a reduction in LLS that can be carried over the time span of one week. In this way, antedated acclimatization may improve safety and comfort on the mountain.

Effects of stomach inflation on haemodynamic and pulmonary function during spontaneous circulation in pigs.

AIM: Stomach inflation during mask ventilation is frequent, but the effects on haemodynamic and pulmonary function are unclear. We evaluated the effects of stomach inflation on haemodynamic and pulmonary function during spontaneous circulation in a porcine model. METHODS: Randomised prospective animal study. After randomisation, in 23 domestic pigs the stomach was inflated every 90s with 0L (control; n=8), 0.5L (n=7) or 1L (n=8) ambient air. RESULTS: After 22.5min, i.e. 8.5L in the 0.5L and 17L in the 1L stomach inflation group, stomach inflation increased central venous pressure (median) (control: 10mmHg vs. 1L: 23mmHg, P<0.05) and mean pulmonary artery pressure (control: 24mmHg vs. 1L: 45mmHg, P<0.05). As a result stroke volume index decreased (control: 135mL/kg vs. 0.5L: 90mL/kg, P<0.05; vs. 1L: 72mL/kg, P<0.05). Stomach inflation also decreased static pulmonary compliance (control: 24mL/cmH(2)O vs. 0.5L: 8mL/cmH(2)O, P<0.05; vs. 1L: 3mL/cmH(2)O, P<0.05), which increased peak airway pressure (control: 28cmH(2)O vs. 0.5L: 69cmH(2)O, P<0.05; vs. 1L: 73cmH(2)O, P<0.05). Additionally, arterial oxygen partial pressure (control: 305mmHg vs. 0.5L: 140mmHg, P<0.05; vs. 1L: 21mmHg, P<0.05) and systemic oxygen delivery (control: 53mLO(2)/min vs. 1L: 19mLO(2)/min, P<0.05) decreased. Stomach inflation increased mortality (control: 0/8 vs. 1L: 5/8, P<0.05). CONCLUSIONS: Stomach inflation with 1L when compared to 0.5L increments resulted in faster haemodynamic and pulmonary failure and increased mortality. Stomach inflation may cause a hyper-acute abdominal compartment syndrome.

Microcirculatory parameters after isotonic and hypertonic colloidal fluid resuscitation in acute hemorrhagic shock.

BACKGROUND: Volume resuscitation is one of the primary therapeutic goals in hemorrhagic shock, but data on microcirculatory effects of different colloidal fluid resuscitation regimen are sparse. We investigated sublingual mucosal microcirculatory parameters during hemorrhage and after fluid resuscitation with gelatin, hydroxyethyl starch, or hypertonic saline and hydroxyethyl starch in pigs. METHODS: To induce hemorrhagic shock, 60% of calculated blood volume was withdrawn. Microvascular blood flow was assessed by laser Doppler velocimetry. Microcirculatory hemoglobin oxygen saturation was measured with a tissue reflectance spectrophotometry, and side darkfield imaging was used to visualize the microcirculation and to quantify the flow quality. Systemic hemodynamic variables, systemic acid base and blood gas variables, and lactate measurements were recorded. Measurements were performed at baseline, after hemorrhage, and after fluid resuscitation with a fixed volume regimen. RESULTS: Systemic hemodynamic parameters returned or even exceeded to baseline values in all three groups after fluid resuscitation, but showed significantly higher filling pressures and cardiac output values in animals treated with isotonic colloids. Microcirculatory parameters determined in gelatin and hydroxyethyl starch resuscitated animals, and almost all parameters except microvascular hemoglobin oxygen saturation in animals treated with hypertonic saline and hydroxyethyl starch, were restored after treatment. DISCUSSION: Hemorrhaged pigs can be hemodynamically stabilized with either isotonic or hypertonic colloidal fluids. The main finding is an adequate restoration of sublingual microcirculatory blood flow and flow quality in all three study groups, but only gelatin and hydroxyethyl starch improved microvascular hemoglobin oxygen saturation, indicating some inadequate oxygen supply/demand ratio maybe due to a better restoration of systemic hemodynamics in isotonic colloidal resuscitated animals.

Pharmacologic Agents for the Treatment of Vasodilatory Shock.

Vasodilatory shock is a life-threatening syndrome in critically ill patients and is characterized by severe hypotension and resultant tissue hypoperfusion. This shock state requires the use of vasopressor agents to restore adequate vascular tone. Norepinephrine is still recommended as first-line vasopressor in the management of critically ill patients suffering from severe vasodilation. In the recent time, catecholaminergic vasopressor drugs have been associated with possible side effects at higher dosages. This so-called catecholamine toxicity has focused on alternative noncatecholaminergic vasopressors or the use of moderate doses of multiple vasopressors with complementary mechanisms of action. Besides vasopressin and terlipressin, angiotensin II may be a promising drug for the management of vasodilatory shock. In addition, adjunctive drugs, such as hydrocortisone, methylene blue or ascorbic acid can be added to conventional vasopressor therapy. The objective of this review is to give an overview of the current available vasopressor agents used in vasodilatory shock. A thorough search of PubMed was conducted in order to identify the majority of studies related to the subject. Data on the outcome of several drugs and future perspective of possible management strategies for the therapy of vasodilatory shock are discussed.

Cutaneous Microvascular Blood Flow and Reactivity in Hypoxia.

As is known, hypoxia leads to an increase in microcirculatory blood flow of the skin in healthy volunteers. In this pilot study, we investigated microcirculatory blood flow and reactive hyperemia of the skin in healthy subjects in normobaric hypoxia. Furthermore, we examined differences in microcirculation between hypoxic subjects with and without short-term acclimatization, whether or not skin microvasculature can acclimatize. Fourty-six healthy persons were randomly allocated to either short-term acclimatization using intermittent hypoxia for 1 h over 7 days at an FiO2 0.126 (treatment, n = 23) or sham short-term acclimatization for 1 h over 7 days at an FiO2 0.209 (control, n = 23). Measurements were taken in normoxia and at 360 and 720 min during hypoxia (FiO2 0.126). Microcirculatory cutaneous blood flow was assessed with a laser Doppler flowmeter on the forearm. Reactive hyperemia was induced by an ischemic stimulus. Measurements included furthermore hemodynamics, blood gas analyses and blood lactate. Microcirculatory blood flow increased progressively during hypoxia (12.3 ± 7.1-19.0 ± 8.1 perfusion units; p = 0.0002) in all subjects. The magnitude of the reactive hyperemia was diminished during hypoxia (58.2 ± 14.5-40.3 ± 27.4 perfusion units; p = 0.0003). Short-term acclimatization had no effect on microcirculatory blood flow. When testing for a hyperemic response of the skin's microcirculation we found a diminished signal in hypoxia, indicative for a compromised auto-regulative circulatory capacity. Furthermore, hypoxic short-term acclimatization did not affect cutaneous microcirculatory blood flow. Seemingly, circulation of the skin was unable to acclimatize using a week-long short-term acclimatization protocol. A potential limitation of our study may be the 7 days between acclimatization and the experimental test run. However, there is evidence that the hypoxic ventilatory response, an indicator of acclimatization, is increased for 1 week after short-term acclimatization. Then again, 1 week is what one needs to get from home to a location at significant altitude.

Arginine vasopressin in advanced cardiovascular failure during the post-resuscitation phase after cardiac arrest.

Arginine vasopressin (AVP) has been employed successfully during cardiopulmonary resuscitation, but there exist only few data about the effects of AVP infusion for cardiovascular failure during the post-cardiac arrest period. Cardiovascular failure is one of the main causes of death after successful resuscitation from cardiac arrest. Although the "post-resuscitation syndrome" has been described as a "sepsis-like" syndrome, there is little information about the haemodynamic response to AVP in advanced cardiovascular failure after cardiac arrest. In this retrospective study, haemodynamic and laboratory variables in 23 patients with cardiovascular failure unresponsive to standard haemodynamic therapy during the post-cardiac arrest period were obtained before, and 30 min, 1, 4, 12, 24, 48, and 72 h after initiation of a supplementary AVP infusion (4 IU/h). During the observation period, AVP significantly increased mean arterial blood pressure (58+/-14 to 75+/-19 mmHg, p < 0.001), and decreased noradrenaline (norepinephrine) (1.31+/-2.14 to 0.23+/-0.3 microg/kg/min, p = 0.03), adrenaline (epinephrine) (0.58+/-0.23 to 0.04+/-0.03 microg/kg/min, p = 0.001), and milrinone requirements (0.46+/-0.15 to 0.33+/-0.22 microg/kg/min, p < 0.001). Pulmonary capillary wedge pressure changed significantly (p < 0.001); an initial increase being followed by a decrease below baseline values. While arterial lactate concentrations (95+/-64 to 21+/-18 mg/dL, p < 0.001) and pH (7.27+/-0.14 to 7.4+/-0.14, p < 0.001) improved significantly, total bilirubin concentrations (1.12+/-0.95 to 3.04+/-3.79 mg/dL, p = 0.001) increased after AVP. There were no differences in the haemodynamic or laboratory response to AVP between survivors and non-survivors. In this study, advanced cardiovascular failure that was unresponsive to standard therapy could be reversed successfully with supplementary AVP infusion in >90% of patients surviving cardiac arrest.

Microcirculatory function monitoring at the bedside--a view from the intensive care.

Microcirculatory dysfunction plays a key role in the pathophysiology of various disease states and may consequently impact patient outcome. Until recently, the evaluation of the microcirculation using different measurement techniques has been mostly limited to animal and human research. With technical advances, microcirculatory monitoring nowadays becomes more and more available for application in clinical praxis. Unfortunately, measurements within the microcirculation are mostly limited to easily accessible surfaces, such as skin, muscle and tongue. Due to major differences in the physiologic regulation of microcirculatory blood flow and in metabolism between organs and even within different tissues in one organ, the clinical importance of regional microcirculatory measurements remains to be determined. In addition, technical methods available demonstrate large differences in the measured parameters and sampling volume, making interpretation of data even more difficult. Nonetheless, the monitoring of the microcirculation may, ahead of time, alert physicians that tissue oxygen supply becomes compromised and it may lead to a better understanding of basic pathophysiological aspects of disease. In the present review, we describe available non-invasive microcirculatory measurement techniques which can be applied clinically at the bedside. After a short discussion of physiologic and pathophysiologic basics related to microcirculatory monitoring, the measuring principles, applications, strengths and limitations of different monitoring systems are discussed.

Arginine vasopressin does not alter mucosal tissue oxygen tension and oxygen supply in an acute endotoxemic pig model.

OBJECTIVE: To determine the effects of increasing dosages of continuously infused arginine-vasopressin (AVP) on mucosal tissue oxygen tension and oxygen supply in an auto-perfused, innervated jejunal segment in an acute endotoxic porcine model. DESIGN: Prospective, randomized, experimental study. SETTING: University hospital animal research laboratory. INTERVENTIONS: Jejunal mucosal tissue PO2 was measured employing two Clark-type surface oxygen electrodes. Oxygen saturation of jejunal microvascular hemoglobin was determined by tissue reflectance spectrophotometry. Systemic hemodynamic variables, mesenteric-venous and systemic acid base and blood gas variables and lactate measurements were recorded. Measurements were performed at baseline, after E. coli lipopolysaccharide (LPS) administration and at 20 min intervals during incremental AVP infusion (n=8; 0.014, 0.029, 0.057, 0.114 and 0.229 IU kg(-1) h(-1), respectively) or infusion of saline (n =8). MEASUREMENTS AND RESULTS: LPS infusion leads to a significant (P<0.05) decrease of mucosal tissue oxygen tension (PO2muc, 24+/-3 to 12+/-2 mmHg) and microvascular hemoglobin oxygen saturation (HbO2, 38+/-4 to 21+/-4%). Mesenteric venous lactate level increased (2.4+/-0.3 to 4.7+/-1.7 mmol l(-1)), while mesenteric venous pH decreased (7.38+/-0.02 to 7.26+/-0.12), indicating tissue hypoxia. AVP significantly increased mean arterial pressure (MAP, 81+/-15 to 97+/-17 at 0.057 IU kg(-1) h(-1)). No differences in jejunal mucosal oxygenation occurred between study groups at any dosage during the experimental protocol. CONCLUSION: AVP administration did not further compromise mucosal tissue oxygen tension and oxygen supply in the acute phase of endotoxic pigs.

Cutaneous vascular reactivity and flow motion response to vasopressin in advanced vasodilatory shock and severe postoperative multiple organ dysfunction syndrome.

INTRODUCTION: Disturbances in microcirculatory homeostasis have been hypothesized to play a key role in the pathophysiology of multiple organ dysfunction syndrome and vasopressor-associated ischemic skin lesions. The effects of a supplementary arginine vasopressin (AVP) infusion on microcirculation in vasodilatory shock and postoperative multiple organ dysfunction syndrome are unknown. METHOD: Included in the study were 18 patients who had undergone cardiac or major surgery and had a mean arterial blood pressure below 65 mmHg, despite infusion of more than 0.5 microg/kg per min norepinephrine. Patients were randomly assigned to receive a combined infusion of AVP/norepinephrine or norepinephrine alone. Demographic and clinical data were recorded at study entry and after 1 hour. A laser Doppler flowmeter was used to measure the cutaneous microcirculatory response at randomization and after 1 hour. Reactive hyperaemia and oscillatory changes in the Doppler signal were measured during the 3 minutes before and after a 5-minute period of forearm ischaemia. RESULTS: Patients receiving AVP/norepinephrine had a significantly higher mean arterial pressure (P = 0.047) and higher milrinone requirements (P = 0.025) than did the patients who received norepinephrine only at baseline. Mean arterial blood pressure significantly increased (P < 0.001) and norepinephrine requirements significantly decreased (P < 0.001) in the AVP/norepinephrine group. Patients in the AVP/norepinephrine group exhibited a significantly higher oscillation frequency of the Doppler signal before ischaemia and during reperfusion at randomization. During the study period, there were no differences in either cutaneous reactive hyperaemia or the oscillatory pattern of vascular tone between groups. CONCLUSION: Supplementary AVP infusion in patients with advanced vasodilatory shock and severe postoperative multiple organ dysfunction syndrome did not compromise cutaneous reactive hyperaemia and flowmotion when compared with norepinephrine infusion alone.

Regional microvascular function and vascular reactivity in patients with different degrees of multiple organ dysfunction syndrome.

The pathophysiology of multiple organ dysfunction syndrome (MODS) is believed to be related to that of microcirculatory dysfunction. We hypothesized that the severity of MODS is determined by measuring regional variables of microvascular function and vascular reactivity in critically ill patients. Therefore, we compared (a) reactive hyperemia response in the forearm using transcutaneous Po2/Pco2 electrodes and laser Doppler velocimetry, (b) microvascular permeability assessed by strain-gauge plethysmography in legs, and (c) variables derived from gastric tonometry in hemodynamically stable patients with moderate (n = 15) and severe (n = 15) MODS. There were no differences in systemic oxygen delivery, consumption, and oxygen extraction ratio between the groups. Mortality was 20% in patients with moderate MODS and 60% in patients with severe MODS (P = 0.025). Patients with a high MODS score had significantly larger arterial lactate concentrations (3.81 +/- 2.7 mmol/L) than patients with moderate MODS (1.66 +/- 0.82 mmol/L; P = 0.006). No significant differences in gastric pHi, gastric regional-to-arterial Pco2 difference, capillary filtration coefficient, isovolumetric venous pressure, and skin reactive hyperemia response were observed between patients with moderate and severe MODS. Once MODS is established, regional variables of microvascular function and vascular reactivity measured in this study do not reflect severity of organ dysfunction.

Arginine vasopressin in advanced vasodilatory shock: a prospective, randomized, controlled study.

BACKGROUND: Vasodilatory shock is a potentially lethal complication of severe disease in critically ill patients. Currently, catecholamines are the most widely used vasopressor agents to support blood pressure, but loss of catecholamine pressor effects is a well-known clinical dilemma. Arginine vasopressin (AVP) has recently been shown to be a potent vasopressor agent to stabilize cardiocirculatory function even in patients with catecholamine-resistant vasodilatory shock. METHODS AND RESULTS: Forty-eight patients with catecholamine-resistant vasodilatory shock were prospectively randomized to receive a combined infusion of AVP and norepinephrine (NE) or NE infusion alone. In AVP patients, AVP was infused at a constant rate of 4 U/h. Hemodynamic, acid/base, single-organ, and tonometrically derived gastric variables were reported before the study and 1, 12, 24, and 48 hours after study entry. For statistical analysis, a mixed-effects model was used. AVP patients had significantly lower heart rate, NE requirements, and incidence of new-onset tachyarrhythmias than NE patients. Mean arterial pressure, cardiac index, stroke volume index, and left ventricular stroke work index were significantly higher in AVP patients. NE patients developed significantly more new-onset tachyarrhythmias than AVP patients (54.3% versus 8.3%). Gastrointestinal perfusion as assessed by gastric tonometry was better preserved in AVP-treated patients. Total bilirubin concentrations were significantly higher in AVP patients. CONCLUSIONS: The combined infusion of AVP and NE proved to be superior to infusion of NE alone in the treatment of cardiocirculatory failure in catecholamine-resistant vasodilatory shock.